The long-term objective of this project is the generation of a universal drug discovery platform based on protein arginine methylation mechanisms involved in human disease. The importance of protein arginine methylation in the context of human disease has become clear in the last few years with the realization that protein arginine methyltransferases and the target proteins for these enzymes are a rich source of potential therapeutic targets. The specific aims of the project are (1) to produce a general high throughput screening method for identifying potent inhibitors of protein arginine methyltransferases and (2) to generate the means for isolating and identifying cellular methylarginine proteins for the purpose of determining the methylation status of specific proteins. The methods include a combination of high throughput screening of enzyme inhibitors and biochemical, immunological, biophysical and cell biology techniques to isolate, identify, quantify and characterize methylarginine protein biomarkers. The final phase of the project will analyze the methylarginine proteins of human blood cells drawn from normal volunteers and patients diagnosed with the autoimmune disease, scleroderma. This research is relevant to millions of Americans afflicted with autoimmune disorders, as well as neurodevelopmental syndromes and viral, neoplastic and cardiovascular disease. Elucidation of the role of protein arginine methylation in these diseases holds promise for better diagnosis, understanding and treatment of health related problems.